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14-3-3 γ-isoform detection distinguishes sporadic Creutzfeldt–Jakob disease from other dementias
  1. B R J Van Everbroeck,
  2. J Boons,
  3. P Cras
  1. Department of Neurobiology, Born Bunge Foundation, University of Antwerp, Wilrijk, Belgium
  1. Correspondence to:
 B Van Everbroeck
 Laboratory of Neurobiology, Born Bunge Foundation (BBS), University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610 Wilrijk, Belgium;


We developed a polyclonal antiserum directed to the γ-isoform of the human 14-3-3 protein and compared the immunoreactivity with a commercially available antibody (CG31). We analysed 14-3-3 in 253 cerebrospinal fluid samples blinded for the diagnosis by western blot and ELISA, with a commonly used polyclonal antiserum (Sc-731) and the γ specific antibodies. Our patient population consisted of 52 patients with definite sporadic Creutzfeldt–Jakob disease (sCJD) and 201 patients with a different final diagnosis. We obtained similar sensitivity, ranging from 96% to 98% with all antibodies. Of all the samples that were false positive with Sc-731, 50% were negative with both γ-isoform specific antibodies resulting in a significantly higher specificity (85% v 93%, respectively). If only sCJD and patients with dementia differing from sCJD were analysed we found that 64% of false positives were negative which also resulted in significantly increased specificity and positive predictive value.

The γ-isoform specific antibodies strongly improve the specificity of the immunoblot and might improve worldwide acceptance of the use of the 14-3-3 assay in the differential diagnosis of sCJD.

  • AA, amino acid
  • AU, arbitrary unit
  • CSF, cerebrospinal fluid
  • ELISA, enzyme linked immunoassay
  • FP, false positives
  • OD, patients with dementia differing from sCJD
  • OND, other neurological disorders
  • sCJD, sporadic Creutzfeldt–Jakob disease
  • TP, true positives
  • cerebrospinal fluid
  • western blot
  • quantification

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  • This study was supported by the Fund for Scientific Research (FWO). BVE is a postdoctoral researcher of the Fund for Scientific Research (FWO).

  • Competing interests: none declared